The present invention relates to sulfate of 1-cyclopropyl-7-(3-methyl-1-piperazinyl)-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (International Nonproprietary Name: gatifloxacin), its use for recovering gatifloxacin and recovering method. Gatifloxacin is characterized by its chemical structure having an alkoxy group at 8-position, and is useful as an antimicrobial agent.
As a method of treating industrial waste liquor containing quinolonecarboxylic acid derivatives, it is common to recover by adsorbing effective ingredients onto synthetic adsorbent etc., or to dispose by directly incinerating waste liquor itself without performing such recovering procedure of the like.
The method of recovering effective ingredients from industrial waste liquor containing quinolonecarboxylic acid derivatives by using synthetic adsorbent etc. is complicated procedurally and not a good method, resulting also in a cause of steep rise in preparation cost. Also, the incinerating disposal of industrial waste liquor containing a large quantity of effective ingredients cannot be said to be a preferable method from the environmental preservation.
Hence, upon preparation of gatifloxacin, it is very useful in the industry to find out a method of advantageously recovering gatifloxacin industrially from waste liquor after preparation and regenerating it.
As a result of diligent investigation on a method of industrially recovering gatifloxacin useful as an antimicrobial agent under such situation, the inventors have found that, if forming sulfate of gatifloxacin in the waste liquor etc., allowing to sediment and separate, and then freeing from salt, gatifloxacin can be advantageously recovered industrially, leading to the completion of the invention.
The inventive gatifloxacin sulfate and its hydrate are novel compounds not described in the literature. The concrete preparing method lies in that aqueous sulfuric acid is added to acidity water or water-containing alcohol dissolved or suspended gatifloxacin, thereby sedimenting sulfate of gatifloxacin. If recrystallizing this further from, for example, water, hydrate of sulfate of gatifloxacin can be obtained.
Also, when recovering gatifloxacin from industrial waste liquor after preparation, aqueous sulfuric acid is added to acidity water-containing alcoholic solution dissolved gatifloxacin, thereby obtaining sulfate as sedimented crystals. These are collected by filtration and washed or recrystallized, and then dissolved or suspended into water. Following this, if the solution is made weak alkaline with aqueous solution of alkali such as sodium hydroxide, good-quality gatifloxacin is freed, thus enabling to recover. In addition, the recycling use is possible by adding sulfate to new preparing process without separating gatifloxacin, leaving as it is in alkaline solution.
Moreover, the alcoholic organic solvent after recovery of gatifloxacin as sulfate can be recovered as a solvent containing no basic ingredients, hence efficient recycling use is possible.